The overall objective of this project is to investigate the relationship between the tissue uptake and distribution of chemotherapeutic agents by the pancreas and pancreatic adenocarcinoma and the antitumor activity of these agents against pancreatic cancer. Two animal pancreatic ductal adenocarcinoma models have been chose to carry out the project in inbred Syrian golden hamsters. The models have been developed and supplied to me courtesy of D.G. Scarpelli and M.S. Rao, Department of Pathology, Northwestern University and include: a) the well-differentiated pancreatic adenocarcinoma (WD PaCa) which is a carcinogen-induced solid tumor model passaged subcutaneously (s.c.) or surgically implanted, and b) the poorly-differentiated pancreatic adenocarcinoma (PD PaCa), which is a spontaneously-arising, ascitic model passaged by intraperitoneal (i.p.) injection. To date, the pharmacologic studies have focused upon Adriamycin (doxorubicin; ADR). Significant findings include a very high uptake of ADR in the normal pancreas of both hamsters and rats. ADR levels achieved in the WD PaCA were quite low compared to normal hamster pancreas or PD PaCa, which had intermediate ADR levels. These differences in ADR uptake may partly explain the difference in sensitivity to ADR between the WD PaCA, which is relatively resistant to ADR, and the PD PaCa, which is sensitive to ADR. Drug sensitivity studies are currently being conducted both in vivo and in vitro (via clonogenic assays). Standard agents are being used first, but studies of experimental drugs are planned. The good correlation between in vivo and in vitro testing suggests that future preliminary screening may be more efficiently performed in vitro. The ultimate goal of this project is to provide information that would lead to more rational and informed clinical trials and to provide a basis for the understanding of the sensitivity and/or resistance of pancreatic cancer to chemotherapy.